This study was conducted to investigate the effects of sex hormones upon the nature of soluble immune response suppressor (SIRS) produced by concanavalin A-stimulated Lyt-2+ T cells. Conventional SIRS affected IgM PFC only. However, SIRS made with progesterone (20-400 ng/ml or Prog-SIRS) suppressed IgM PFC, one-way MLR, and generation CTL; and SIRS made with estrogen (0.2-50 ng/ml or Est-SIRS) enhanced these responses. The factor(s) (MW 40,000-55,000) to stimulate macrophages to produce the second soluble factor (M phi-SF) was isolated from all preparations by gel filtration. Furthermore, Est-SIRS contained a factor(s) (MW 10,000-30,000) to enhance IgM PFC, MLR, and mitogen-induced blastogenesis of both T and B cells; and Prog-SIRS possessed the suppressive factor(s) to IgM PFC, MLR, and mitogen-induced T-cell proliferation. These activities were not impaired by 2-mercaptoethanol. Moreover, the suppressive activity of Prog-SIRS was completely absorbed by T cells only, but the enhancing activity of Est-SIRS was not completely absorbed by a single-cell population. These data suggest that progesterone can contribute to the suppression of allograft rejection through soluble factors, and estrogen can enhance host responses which may be affected by several soluble factors during pregnancy.